In the brain, oligodendrocytes form myelin sheaths around axons to insulate signal conduction. In certain neurological disorders such as multiple sclerosis, the degeneration of myelin sheaths can induce disabilities in patients. Therefore, developing myelin or myelin-related biomarkers has important clinical values for the diagnosis and prognosis of such diseases. Several MRI methods including myelin water imaging (Mackay, et al., 1994, In vivo visualization of myelin water in brain by magnetic resonance. Magn Reson Med 31, 673-677), magnetization transfer imaging (Balaban, et al., 1992, Magnetization transfer contrast in magnetic resonance imaging. Magn Reson Q 8, 116-137; Gass, et al., 1994, Correlation of magnetization transfer ration with clinical disability in multiple sclerosis, Ann Neurol 36, 62-67), and diffusion tensor imaging (Basser, et al., 1994, MR diffusion tensor spectroscopy and imaging. Biophys J 66, 259-267; Werring, et al., 1999, Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis, Neurology 52, 1626-1626) have been proposed as potential biomarkers for myelin. Among these, myelin water imaging (MWI) measures signals from water molecules in the gap between neighboring myelin layers in white matter. It has been suggested that this fraction of water has more rapid transverse (Du, et al., 2007, Fast multislice mapping of the myelin water fraction using multicompartment analysis of T2* decay at 3 T: a preliminary postmortem study, Magn Reson Med 58, 865-870; Mackay 1994; Menon, et al., 1991, Application of continuous relaxation time distributions to the fitting of data from model systems and excised tissue, Magn Reson Med 20, 214-227; van Gelderen, et al., 2012. Nonexponential T2* decay in white matter, Magn Reson Med 67, 110-117; Vasilescu, et al., 1978, Water compartments in the myelinated nerve. III. Pulsed NMR result, Experientia 34, 1443-1444) and longitudinal relaxations (Does, et al., 2002, Compartmental study of T1 and T2 in rat brain and trigeminal nerve in vivo, Magn Reson Med 47, 274-283; Koenig, et al., 1990, Relaxometry of brain: why white matter appears bright in MRI, Magn Reson Med 14, 482-495; Labadie, et al., 2009, Comparison of myelin water fraction in cross-regularized T1-relaxograms of normal white matter at 3 T and 7 T and of normal-appearing white matter at 3 T, Proceedings of the 17th Annual Meeting of ISMRM, Honolulu, Hi., p. 3210; Lancaster, et al., 2002, Three-pool model of white matter, J Magn Reson Imaging 17, 1-10; Stanisz, et al., 2005, T1, T2 relaxation and magnetization transfer in tissue at 3 T, Magn Reson Med 54, 507-512) than other water inside of axons or in the extracellular space outside of fibers. In conventional MWI, the transverse relaxations are measured by multi-echo GRE or SE sequences. Since the multiple water components have different relaxations, the measured signal shows a multi-exponential decay. This decay is fitted with exponential decay basis functions to estimate the distribution of transverse relaxations (Whittall, et al., 1989, Quantitative interpretation of NMR relaxation data. JMR 84, 134-152). Then, the fraction of the short transverse relaxation component or myelin water, which is approximately in the range of T2<40 ms and T2*<25 ms at 3 T (Hwang, et al., 2010, In vivo multi-slice mapping of myelin water content using T2* decay, NeuroImage 52, 198-204; Kolind, et al., 2009, Myelin water imaging: implementation and development at 3.0 T and comparison to 1.5 T measurements, Magn Reson Med 62, 106-115; Oh, et al., 2006, Measurement of in vivo multi-component T2 relaxation times for brain tissue using multi-slice T2 prep at 1.5 and 3 T, Magn Reson Imaging 24, 33-43), relative to the total water is calculated to generate a myelin water image. However, the fitting process is ill-conditioned and the resulting MWI is sensitive to noise and artifacts (Cover, K. S., 2008, A robust and reliable method for detecting signals of interest in multiexponential decays, Rev Sci Instrum 79, 055106-055101 055106-055111; Whittall, et al., 1989).
An MRI pulse sequence sensitive to myelin water, a potential biomarker for myelin, is desired that better distinguishes between the bound water between myelin layers and water found in edema or inflammation, which contains a high component of free water. More generally, an improved technique for myelin water imaging is desired that better distinguishes the bound water between myelin layers and the other water in the brain.